1. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;2. ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal;3. Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil;4. Department of Pathology of the School of Medicine of the Federal University of Goiás, Brazil;5. Laboratory of Medical Investigation (LIM) 14, Faculty of Medicine, São Paulo State University, Brazil.

Abstract

Persistent HPV infection alone is not sufficient for cervical cancer development, which requires additional molecular alterations for tumor progression and metastasis ultimately leading to a lethal disease. In this study, we performed a comprehensive analysis of HER family receptor alterations in cervical adenocarcinoma. We detected overexpression of HER protein, mainly HER2, which was an independent prognostic marker for these patients. By using in vitro and in vivo approaches, we provided evidence that HER inhibitors, allitinib and lapatinib, were effective in reducing cervical cancer aggressiveness. Furthermore, combination of these drugs with glucose uptake blockers could overcome the putative HIF1-α-mediated resistance to HER-targeted therapies. Thus, we propose that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients.